CSF1R-IN-22
CSF1R-IN-22 (Compound C19) is an orally effective CSF-1R selective inhibitor (IC50<6 nM). CSF1R-IN-22 enhances the secretion of CXCL9 from M2 macrophages, increases CD8+ T cell infiltration. CSF1R-IN-22 boosts anti-tumor immune responses of anti-PD-1, and induces apoptosis in tumor cells. CSF1R-IN-22 can effectively reprogram M2-like TAMs (tumor-associated macrophages) to the M1 phenotype and reshape the TME by inducing the recruitment of CD8+ T cells into tumors and reducing the infiltration of immunosuppressive Tregs and MDSCs.
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- CAS No.: 2760585-35-9
- Formule: C20H20N6O3
- Masse moléculaire:392.41
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
CSF1R-IN-22 (0-2500 nM; 1 h) significantly inhibits the activation of CSF-1R signaling pathway in BMDMs cells[1].
CSF1R-IN-22 (30-100 nM; 24 h) efficiently reprograms M2-type macrophages to M1-type macrophages in BMDMs and HMDMs cells[1].
CSF1R-IN-22 (10-100 nM; 20 h) processed M2-type macrophage supernatants significantly inhibits MC-38 and CT-26 cell viability[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:BMDMs cells
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Concentration:10, 30, 100 nM
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Incubation Time:1 h
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Result:Dose-dependently inhibited the phosphorylation of CSF-1R and its downstream signaling mediators AKT and mTORC1.
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Cell Line:MC-38, CT-26 cells
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Concentration:10, 30, 100 nM
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Incubation Time:20 h
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Result:Processed M2 macrophage supernatant significantly increased the apoptosis rate of MC-38 and CT-26 cells, with an increase of approximately 60% in the 100 nM concentration group.
CSF1R-IN-22 (20 mg/kg; p.o.; once daily for 14 days) shows stronger anti-tumor effects when combined with 100 μg/mouse PD-1 antibody.CXCL9 expression is significantly positively correlated with survival[1].
Pharmacokinetic Analysis in SD rats[1]
| Route | Dose (mg/kg) | AUC0-t (ng·h/mL) | t1/2 (h) | Cl (L/h/kg) | Vss (L/kg) | Cmax (ng/mL) | F (%) |
| i.v. | 1 | 9126.62 | 1.34 | 0.10 | 0.34 | / | / |
| p.o. | 10 | 85 939.36 | 2.41 | 0.12 | / | 10 867.65 | 94.2 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice bearing subcutaneous MC-38 tumors [1]
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Dosage:5,10,20 mg/kg
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Administration:p.o.; once daily for 14 days
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Result:Inhibited tumor growth, tumor mass was significantly lower than that of the control group, and induced apoptosis. In the high-dose group, tumor volume inhibition (TGI) was 65% and 30-day survival in mice was 70%.
Increased mRNA levels of M1 macrophage markers (Nos2, Tnf, Il6, Il1) and decreased expression of M2 macrophage markers (Arg1, Chil3l, Rentla, Mrc1).
(10 mg/kg and 20 mg/kg) Significantly increased the proportion of CD3+ CD8+ T cells. Dose-dependently reduced the proportion of immunosuppressive Treg cells and myeloid-derived suppressor cells (MDSCs) in tumor tissues.
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Animal Model:C57BL/6 mice bearing subcutaneous MC-38 tumors or MC-38-luc [1]
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Dosage:20 mg/kg; 100 μg/mouse PD-1
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Administration:p.o.; once daily for 14 days
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Result:Significantly lower tumor bioluminescence intensity in the combination dose group than in the PD-1 antibody alone or C19 alone dose groups in both models.
The combination dose group significantly increased the proportion of CD3+ CD8+ T cells and CTLs in the tumor tissue while significantly decreasing the proportion of immunosuppressive Treg cells in the MC-38 tumor model. A significant increase in the infiltration of CD8+ T cells and CTLs correlated with a significant increase in the mRNA expression of Cxcl9.
Co-administered mice had 100% survival at 70 days, and 70% overcame tumor recurrence within 91 days after reinoculation with MC-38 tumor cells.
A significant reduction in apoptosis and a significant reduction in the proportion of CD3+ CD8+ T cells following the use of CXCL9-neutralizing antibody.
Chemical Information
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CAS No. 2760585-35-9
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Masse moléculaire 392.41
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Formule C20H20N6O3
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SMILES
CC(C)(C1=CC(NC(NC2=CC(NC/3=O)=C(C=C2)C3=C\C4=CN=CN4)=O)=NO1)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CSF1R-IN-22 Related Classifications
HY-162415 Related Classifications
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